Objective
Ferroptosis is a cell death modality triggered by the accumulation of oxidised lipids, a process known as lipid oxidation, and associated with a multitude of pathological conditions, including ageing, neurodegeneration, and cancer. On the flip side, recent studies demonstrated that targeting pathways contributing to the prevention or repair of oxidised lipids is a powerful strategy to eradicate therapeutically challenging entities, including neuroblastoma, a pediatric malignancy reported to be remarkably sensitive to ferroptosis. However, therapeutic breakthroughs targeting this pathway are elusive due to our incomplete understanding of the factors controlling this process. DeciFERR will address this critical knowledge gap and identify strategies to trigger ferroptosis. This will be accomplished by discovering and characterising novel mechanisms regulating the stability of key ferroptosis suppressors, thus providing opportunities to develop tailored strategies to target ferroptosis-sensitive entities.
This project rests on our pioneering works identifying two major break systems operating against lipid peroxidation, glutathione peroxidase 4(GPX4) and ferroptosis suppressor protein 1 (FSP1). In Aim 1, using a combination of novel cellular model and target-oriented phenotypic screens, we will characterise and target pathways involved in selenocysteine uptake, mobilisation and recycling, which we found essential for the stability of selenoproteins, including GPX4. In Aim 2, we will dissect metabolic and cellular states that determine the antioxidant capacity of membranes via FSP1-dependent mechanisms using a combination of cellular systems and functional genetic screens. DeciFERR will lead to a comprehensive understanding of how ferroptosis is orchestrated and will expand the druggable inventory, providing innovative strategies that will be put to test and could ultimately pave the way for efficacious therapies against malignancies that still defy current treatments.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- engineering and technology environmental engineering waste management waste treatment processes recycling
- natural sciences chemical sciences electrochemistry electrolysis
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
97070 Wuerzburg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.